Methods of evaluating individuals having reversible obstructive pulmonary disease

ABSTRACT

This relates to treating an asthmatic lung and more particularly, relates to advancing a treatment device into the lung and treating the lung with the device. This also includes additional steps of treating the airway wall, applying energy or heat to the airway wall in an asthmatic lung.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a Continuation of U.S. application Ser. No.11/557,309, filed Nov. 7, 2006, now U.S. Pat. No. 7,992,572, which is aContinuation-in-part of U.S. application Ser. No. 10/640,967, filed Aug.13, 2003, now U.S. Pat. No. 7,273,055, which is a Continuation of U.S.application Ser. No. 09/535,856, filed Mar. 27, 2000, now U.S. Pat. No.6,634,363, which is a Continuation-in-part of U.S. application Ser. No.09/296,040, filed Apr. 21, 1999, now U.S. Pat. No. 6,411,852, which is aContinuation-in-part of U.S. application Ser. No. 09/095,323, filed Jun.10, 1998; U.S. application Ser. No. 10/640,967, now U.S. Pat. No.7,273,055, is also a Continuation-in-part of U.S. application Ser. No.09/436,455, filed Nov. 8, 1999, now U.S. Pat. No. 7,425,212, which is aContinuation-in-part of U.S. application Ser. No. 09/095,323, filed Jun.10, 1998, and a Continuation-in-part of U.S. application Ser. No.09/349,715, filed Jul. 8, 1999, now U.S. Pat. No. 6,488,673. All of theabove applications are incorporated by referenced herein in theirentirety.

BACKGROUND OF THE INVENTION

The invention relates to a method of treating a lung having at least onesymptom of reversible obstructive pulmonary disease, and moreparticularly, the invention relates to advancing a treatment device intothe lung and treating the lung with the device to at least reduce theability of the lung to produce at least one of the symptoms ofreversible obstructive pulmonary disease. The invention includesadditional steps that reduce the ability of the lung to produce at leastone of the symptoms of reversible obstructive pulmonary disease and toreduce the resistance to the flow of air through a lung.

Reversible obstructive pulmonary disease includes asthma and reversibleaspects of chronic obstructive pulmonary disease (COPD). Asthma is adisease in which (i) bronchoconstriction, (ii) excessive mucusproduction, and (iii) inflammation and swelling of airways occur,causing widespread but variable airflow obstruction thereby making itdifficult for the asthma sufferer to breathe. Asthma is a chronicdisorder, primarily characterized by persistent airway inflammation.However, asthma is further characterized by acute episodes of additionalairway narrowing via contraction of hyper-responsive airway smoothmuscle.

The reversible aspects of COPD generally describe excessive mucusproduction in the bronchial tree. Usually, there is a general increasein bulk (hypertrophy) of the large bronchi and chronic inflammatorychanges in the small airways. Excessive amounts of mucus are found inthe airways and semisolid plugs of mucus may occlude some small bronchi.Also, the small airways are narrowed and show inflammatory changes. Thereversible aspects of COPD include partial airway occlusion by excesssecretions, and airway narrowing secondary to smooth muscle contraction,bronchial wall edema and inflation of the airways

In asthma, chronic inflammatory processes in the airway play a centralrole in increasing the resistance to airflow within the lungs. Manycells and cellular elements are involved in the inflammatory process,particularly mast cells, eosinophils T lymphocytes, neutrophils,epithelial cells, and even airway smooth muscle itself. The reactions ofthese cells result in an associated increase in the existing sensitivityand hyper-responsiveness of the airway smooth muscle cells that line theairways to the particular stimuli involved.

The chronic nature of asthma can also lead to remodeling of the airwaywall (i.e., structural changes such as thickening or edema) which canfurther affect the function of the airway wall and influence airwayhyper-responsiveness. Other physiologic changes associated with asthmainclude excess mucus production, and if the asthma is severe, mucusplugging, as well as ongoing epithelial denudation and repair.Epithelial denudation exposes the underlying tissue to substances thatwould not normally come in contact with them, further reinforcing thecycle of cellular damage and inflammatory response.

In susceptible individuals, asthma symptoms include recurrent episodesof shortness of breath (dyspnea), wheezing, chest tightness, and cough.Currently, asthma is managed by a combination of stimulus avoidance andpharmacology.

Stimulus avoidance is accomplished via systematic identification andminimization of contact with each type of stimuli. It may, however, beimpractical and not always helpful to avoid all potential stimuli.

Asthma is managed pharmacologically by: (1) long term control throughuse of anti-inflammatories and long-acting bronchodilators and (2) shortterm management of acute exacerbations through use of short-actingbronchodilators. Both of these approaches require repeated and regularuse of the prescribed drugs. High doses of corticosteroidanti-inflammatory drugs can have serious side effects that requirecareful management. In addition, some patients are resistant to steroidtreatment. The difficulty involved in patient compliance withpharmacologic management and the difficulty of avoiding stimulus thattriggers asthma are common barriers to successful asthma management.

Asthma is a serious disease with growing numbers of sufferers. Currentmanagement techniques are neither completely successful nor free fromside effects.

Accordingly, it would be desirable to provide an asthma treatment whichimproves airflow without the need for patient compliance.

In addition to the airways of the lungs, other body conduits such as theesophagus, ureter, urethra, and coronary arteries, are also subject toperiodic reversible spasms that produce obstruction to flow.

SUMMARY OF THE INVENTION

The present invention relates to methods for treating a lung, preferablyhaving at least one symptom of reversible obstructive pulmonary disease,comprising the steps of advancing a treatment device into the lung andtreating the lung with the device to at least reduce the ability of thelung to produce at least one symptom of reversible obstructive pulmonarydisease and to decrease the resistance to the flow of air through thelung.

A variation of the invention includes the method described above furthercomprising the step of locating one or more treatment sites within anairway of the lung, selecting at least one of the treatment sites andtreating at least one of the treatment sites selected in the selectingstep. The invention may further include performing the steps while thelung is experiencing at least one symptom of either natural orartificially induced reversible obstructive pulmonary disease.

A further variation of the invention includes the method described aboveand further includes the steps of testing the lung for at least onepre-treatment pulmonary function value prior to the treating step, andre-testing the lung for at least one post-treatment pulmonary functionvalue subsequent to the treating step.

A further variation of the invention includes the method described abovefurther comprising identifying treatment sites within the airway beinghighly susceptible to either airway inflammation, airway constriction,excessive mucus secretion, or any other symptom of reversibleobstructive pulmonary disease.

Another variation of the invention includes the method described aboveand the additional step of stimulating the lung to produce at least oneartificially induced symptom of reversible obstructive pulmonarydisease. The invention may further comprise the step of evaluating theresults of the stimulating step.

Another variation of the invention includes the method described abovewhere treating at least airway tissue within the lung further comprisesthe step of determining the effect of the treatment by visuallyobserving the airway for blanching of airway tissue.

Another variation of the invention includes the method described abovewhere treating at least airway tissue at a treatment site within thelung further comprises the step of monitoring electrical impedance oftissue at one or more points.

Another variation of the invention includes the method described abovewhere treating the lung includes sub-mucosal treatment of at leastairway tissue in the lung.

Another variation of the invention includes the method described abovewhere the treating step includes treating the lung by depositing aradioactive substance in at least one treatment site within the lung.

Another variation of the invention include the method described abovefurther including the step of scraping tissue from a wall of an airwaywithin the lung prior to the treating step. The invention may furthercomprise depositing a substance on the scraped wall of the airway.

Another variation of the invention includes the method described abovewhere the treating step uses a modality selected from the groupconsisting of mechanical, chemical, radio frequency, radioactive energy,heat, and ultrasound.

Another variation of the invention includes the method described abovefurther comprising pre-treating the lung to at least reduce the abilityof the lung to produce at least one symptom of reversible obstructivepulmonary disease prior to the treating step, where at least oneparameter of the pre-treating step is lesser than at least one parameterof the treating step.

Another variation of the invention comprises the method described abovewhere the treating step includes separating the treating step intostages to reduce the healing load on the lung. The separating step maycomprise treating different regions of the lung at different times ordividing the number of treatment sites into a plurality of groups oftreatment sites and treating each group at a different time.

Another variation of the invention includes the method described abovefurther comprising sensing movement of the lung and repositioning thetreatment device in response to said sensing step.

Another variation of the invention includes the method described abovefurther comprising reducing the temperature of lung tissue adjacent to atreatment site.

Another variation of the invention includes the method described abovefurther comprising the step of providing drug therapy, exercise therapy,respiratory therapy, and/or education on disease management techniquesto further reduce the effects of reversible obstructive pulmonarydisease.

The invention further includes the method for reversing a treatment toreduce the ability of the lung to produce at least one symptom ofreversible obstructive pulmonary disease comprising the step ofstimulating re-growth of smooth muscle tissue in the lung.

The invention further includes the method of evaluating an individualhaving reversible obstructive pulmonary disease as a candidate for aprocedure to reduce the ability of the individual's lung to produce atleast one reversible obstructive pulmonary disease symptom by treatingan airway within the lung of the individual, the method comprising thesteps of assessing the pulmonary condition of the individual, comparingthe pulmonary condition to a corresponding predetermined state; andevaluating the individual based upon the comparing step. The method mayadditionally comprise the steps of performing pulmonary function testson the individual to obtain at least one pulmonary function value,comparing the at least one pulmonary function value to a correspondingpredetermined pulmonary function value, and evaluating the individualbased upon the comparing step.

The invention further comprises a method of evaluating the effectivenessof a procedure to reduce the ability of lung to produce at least onesymptom of reversible obstructive pulmonary disease previously performedon an individual having reversible obstructive pulmonary disease, themethod comprising the steps of assessing the pulmonary condition of theindividual, comparing the pulmonary condition to a correspondingpredetermined state; and evaluating the effectiveness of the procedurebased upon the comparing step. The method may additionally comprise thesteps of performing pulmonary function tests on the individual to obtainat least one pulmonary function value, treating the lung to at leastreduce the ability of the lung to produce at least one symptom ofreversible obstructive pulmonary disease, performing post-procedurepulmonary function tests on the individual to obtain at least onepost-procedure pulmonary function value; and comparing the pulmonaryfunction value with the post-procedure pulmonary function value todetermine the effect of the treating step.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will now be described in greater detail with reference tothe various embodiments illustrated in the accompanying drawings:

FIG. 1. is a cross sectional view of an airway in a healthy lung.

FIG. 2. shows a section through a bronchiole having an airway diametersmaller than that shown in FIG. 1.

FIG. 3 illustrates the airway of FIG. 1 in which the smooth muscle 14has hypertrophied and increased in thickness causing reduction of theairway diameter.

FIG. 4 is a schematic side view of the lungs being treated with atreatment device 38 as described herein.

DETAILED DESCRIPTION

The invention relates to methods for improving airflow through theairways of a lung having reversible obstructive pulmonary disease. It isintended that the invention is applicable to any aspect of reversibleobstructive pulmonary disease, including but not limited to asthma. Oneway of improving airflow is to decrease the resistance to airflow withinthe lungs. There are several approaches to reducing this resistance,including but not limited to reducing the ability of the airway tocontract, increasing the airway diameter, reducing the inflammation ofairway tissues, and/or reducing the amount of mucus plugging of theairway. The present invention includes advancing a treatment device intothe lung and treating the lung to at least reduce the ability of thelung to produce at least one symptom of reversible obstructive pulmonarydisease. The following is a brief discussion of some causes of increasedresistance to airflow within the lungs and the inventive treatment ofthe invention described herein. As such, the following discussion is notintended to limit the aspects or objective of the inventive method asthe inventive method may cause physiological changes not described belowbut such changes still contributing to reducing or eliminating at leastone of the symptoms of reversible obstructive pulmonary disease.

Reducing the Ability of the Airway to Contract

The inventive treatment reduces the ability of the airways to narrow orto reduce in diameter due to airway smooth muscle contraction. Theinventive treatment uses a modality of treatments including, but notlimited to the following: chemical, radio frequency, radioactivity,heat, ultrasound, radiant, laser, microwave, or mechanical energy (suchas in the form of cutting, punching, abrading, rubbing, or dilating).This treatment reduces the ability of the smooth muscle to contractthereby lessening the severity of an asthma attack. The reduction in theability of the smooth muscle to contract may be achieved by treating thesmooth muscle itself or by treating other tissues which in turninfluence smooth muscle contraction or the response of the airway to thesmooth muscle contraction. Treatment may also reduce airwayresponsiveness or the tendency of the airway to narrow or to constrictin response to a stimulus.

The amount of smooth muscle surrounding the airway can be reduced byexposing the smooth muscle to energy which either kills the muscle cellsor prevents these cells from replicating. The reduction in smooth musclereduces the ability of the smooth muscle to contract and to narrow theairway during a spasm. The reduction in smooth muscle and surroundingtissue has the added potential benefit of increasing the caliber ordiameter of the airways, this benefit reduces the resistance to airflowthrough the airways. In addition to the use of debulking smooth muscletissue to open up the airways, the device used in the present inventionmay also eliminate smooth muscle altogether by damaging or destroyingthe muscle. The elimination of the smooth muscle prevents thecontraction or spasms of hyper-reactive airways of a patient havingreversible obstructive pulmonary disease. By doing so, the eliminationof the smooth muscle may reduce some symptoms of reversible obstructivepulmonary disease.

The ability of the airway to contract can also be altered by treatmentof the smooth muscle in particular patterns. The smooth muscle isarranged around the airways in a generally helical pattern with pitchangles ranging from about −38 to about +38 degrees. Thus, the treatmentof the smooth muscle in appropriate patterns interrupts or cuts throughthe helical pattern of the smooth muscle at a proper pitch and preventsthe airway from constricting. This procedure of patterned treatmentapplication eliminates contraction of the airways without completelyeradicating smooth muscle and other airway tissue. A pattern fortreatment may be chosen from a variety of patterns includinglongitudinal or axial stripes, circumferential bands, helical stripes,and the like as well as spot patterns having rectangular, elliptical,circular or other shapes. The size, number, and spacing of the treatmentbands, stripes, or spots are chosen to provide a desired clinical effectof reduced airway responsiveness while limiting insult to the airway toa clinically acceptable level.

The patterned treatment of the tissues surrounding the airways withenergy provides various advantages. The careful selection of the portionof the airway to be treated allows desired results to be achieved whilereducing the total healing load. Patterned treatment can also achievedesired results with decreased morbidity, preservation of epithelium,and preservation of a continuous or near continuous ciliated innersurface of the airway for mucociliary clearance. The pattern oftreatment may also be chosen to achieve desired results while limitingtotal treatment area and/or the number of airways treated, therebyimproving speed and ease of treatment.

Application of energy to the tissue surrounding the airways may alsocause the DNA of the cells to become cross linked. The treated cellswith cross linked DNA are incapable of replicating. Accordingly, overtime, as the smooth muscle cells die, the total thickness of smoothmuscle decreases because of the inability of the cells to replicate. Theprogrammed cell death causing a reduction in the volume of tissue iscalled apoptosis. This treatment does not cause an immediate effect butcauses shrinking of the smooth muscle and opening of the airway overtime and substantially prevents re-growth. The application of energy tothe walls of the airway may also be used to cause a cross linking of theDNA of the mucus gland cells thereby preventing them from replicatingand reducing excess mucus plugging or production over time.

The ability of the airways to contract may also be reduced by alteringmechanical properties of the airway wall, such as by increasingstiffness of the wall or by increasing parenchymal tethering of theairway wall. Both of these methods increase the strength of the airwaywall and further oppose contraction and narrowing of the airway.

There are several ways to increase the stiffness of the airway wall. Oneway to increase stiffness is to induce fibrosis or a wound healingresponse by causing trauma to the airway wall. The trauma can be causedby delivery of therapeutic energy to the tissue in the airway wall, bymechanical insult to the tissue, or by chemically affecting the tissue.The energy is preferably delivered in such a way that it minimizes orlimits the intra-luminal thickening that may occur.

Another way to increase the effective stiffness of the airway wall is toalter the submucosal folding of the airway upon narrowing. The mucosallayer includes the epithelium, its basement membrane, and the laminapropria, a subepithelial collagen layer. The submucosal layer may alsoplay a role in airway folding. As an airway narrows, its perimeterremains relatively constant, with the mucosal layer folding upon itself.As the airway narrows further, the mucosal folds mechanically interferewith each other, effectively stiffening the airway. In asthmaticpatients, the number of folds is fewer and the size of the folds islarger, and thus, the airway is free to narrow with less mechanicalinterference of mucosal folds than in a healthy patient. Thus, asthmaticpatients have a decrease in airway stiffness and the airways have lessresistance to narrowing.

The mucosal folding in asthmatic patients can be improved by treatmentof the airway in a manner which encourages folding. Preferably, atreatment will increase the number of folds and/or decrease the size ofthe folds in the mucosal layer. For example, treatment of the airwaywall in a pattern such as longitudinal stripes can encourage greaternumber of smaller mucosal folds and increase airway stiffness.

The mucosal folding can also be increased by encouraging a greaternumber of smaller folds by reducing the thickness of the mucosa and/orsubmucosal layer. The decreased thickness of the mucosa or submucosa maybe achieved by application of energy which either reduces the number ofcells in the mucosa or submucosal layer or which prevents replication ofthe cells in the mucosa or submucosal layer. A thinner mucosa orsubmucosal layer will have an increased tendency to fold and increasedmechanical stiffening caused by the folds.

Another way to reduce the ability of the airways to contract is toimprove parenchymal tethering. The parenchyma surrounds airways andincludes the alveolus and tissue connected to and surrounding the outerportion of the airway wall. The parenchyma includes the alveolus andtissue connected to and surrounding the cartilage that supports thelarger airways. In a healthy patient, the parenchyma provides a tissuenetwork which connects to and helps to support the airway. Edema oraccumulation of fluid in lung tissue in patients with asthma or COPD isbelieved to decouple the airway from the parenchyma reducing therestraining force of the parenchyma which opposes airway constriction.Energy can be used to treat the parenchyma to reduce edema and/orimprove parenchymal tethering.

In addition, the applied energy may be used to improve connectionbetween the airway smooth muscle and submucosal layer to the surroundingcartilage, and to encourage wound healing, collagen deposition, and/orfibrosis in the tissue surrounding the airway to help support the airwayand prevent airway contraction.

Increasing the Airway Diameter

Hypertrophy of smooth muscle, chronic inflammation of airway tissues,and general thickening of all parts of the airway wall can reduce theairway diameter in patients with reversible obstructive pulmonarydisease. Increasing the overall airway diameter using a variety oftechniques can improve the passage of air through the airways.Application of energy to the airway smooth muscle of an asthmaticpatient can debulk or reduce the volume of smooth muscle. This reducedvolume of smooth muscle increases the airway diameter for improved airexchange.

Reducing inflammation and edema of the tissue surrounding the airway canalso increase the diameter of an airway. Inflammation and edema(accumulation of fluid) of the airway are chronic features of asthma.The inflammation and edema can be reduced by application of energy tostimulate wound healing and regenerate normal tissue. Healing of theepithelium or sections of the epithelium experiencing ongoing denudationand renewal allows regeneration of healthy epithelium with lessassociated airway inflammation. The less inflamed airway has anincreased airway diameter both at a resting state and in constriction.The wound healing can also deposit collagen which improves parenchymaltethering.

Inflammatory mediators released by tissue in the airway wall may serveas a stimulus for airway smooth muscle contraction. Therapy that reducesthe production and release of inflammatory mediator can reduce smoothmuscle contraction, inflammation of the airways, and edema. Examples ofinflammatory mediators are cytokines, chemokines, and histamine. Thetissues which produce and release inflammatory mediators include airwaysmooth muscle, epithelium, and mast cells. Treatment of these structureswith energy can reduce the ability of the airway structures to produceor release inflammatory mediators. The reduction in releasedinflammatory mediators will reduce chronic inflammation, therebyincreasing the airway inner diameter, and may also reducehyper-responsiveness of the airway smooth muscle.

A further process for increasing the airway diameter is by denervation.A resting tone of smooth muscle is nerve regulated by release ofcatecholamines. Thus, by damaging or eliminating nerve tissue in theairways the resting tone of the smooth muscle is reduced, and the airwaydiameter is increased. Resting tone may also be reduced by directlyaffecting the ability of smooth muscle tissue to contract.

Reducing Plugging of the Airway

Excess mucus production and mucus plugging are common problems duringboth acute asthma exacerbation and in chronic asthma management. Excessmucus in the airways increases the resistance to airflow through theairways by physically blocking all or part of the airway. Excess mucusmay also contribute to increased numbers of leukocytes found in airwaysof asthmatic patients by trapping leukocytes. Thus, excess mucus canincrease chronic inflammation of the airways.

One type of asthma therapy involves treatment of the airways with energyto target and reduce the amount of mucus producing cells and glands andto reduce the effectiveness of the remaining mucus producing cells andglands. The treatment can eliminate all or a portion of the mucusproducing cells and glands, can prevent the cells from replicating orcan inhibit their ability to secrete mucus. This treatment will haveboth chronic benefits in increasing airflow through the airways and willlessen the severity of acute exacerbation of the symptoms of reversibleobstructive pulmonary disease.

Illustrated below are different treatment devices for transferringenergy into the airways. Described below are just some of the examplesof the type of treatment devices which may be used to treat airwaytissue according to the present disclosure. It should be recognized thateach of the treatment devices described below can be modified to deliveror to remove energy in different patterns depending on the treatment tobe performed. The treatment devices may be actuated continuously for apredetermined period while stationary. may be pulsed, may be actuatedmultiple times as they are moved along an airway, may be operatedcontinuously while moving the device in an airway to achieve a“painting” of the airway, or may be actuated in a combination of any ofthese techniques. The particular energy application pattern desired canbe achieved by configuring the treatment device itself or by moving thetreatment device to different desired treatment locations in the airway.

Application of Treatment

The following illustrations are examples of the invention describedherein. It is contemplated that combinations of aspects of specificembodiments or combinations of the specific embodiments themselves arewithin the scope of this disclosure.

FIGS. 1 and 2 illustrate cross sections of two different airways in ahealthy patient. The airway of FIG. 1 is a medium sized bronchus havingan airway diameter D1 of about 3 mm. FIG. 2 shows a section through abronchiole having an airway diameter D2 of about 1.5 mm. Each airwayincludes a folded inner surface or epithelium 10 surrounded by stroma 12and smooth muscle tissue 14. The larger airways including the bronchusshown in FIG. 1 also have mucous glands 16 and cartilage 18 surroundingthe smooth muscle tissue 14. Nerve fibers 20 and blood vessels 24 alsosurround the airway.

FIG. 3 illustrates the bronchus of FIG. 1 in which the smooth muscle 14has hypertrophied and increased in thickness causing the airway diameterto be reduced from the diameter D1 to a diameter D3.

FIG. 4 is a schematic side view of the lungs being treated with atreatment device 38 according to the present invention. The treatmentdevice 38 is an elongated member for treating tissue at a treatment site34 within a lung. Although the invention discusses treatment of tissueat the surface it is also intended that the invention include treatmentbelow an epithelial layer of the lung tissue.

An example of devices for use with the methods of this invention arefound in the following U.S. patent application Ser. No.09/095,323—Methods and Apparatus for Treating Smooth Muscles in theWalls of Body Conduits; Ser. No. 09/349,715—Method of Increasing GasExchange of a Lung now U.S. Pat. No. 6,488,675; and Ser. No.09/296,040—Devices for Modification of Airways By Transfer of Energy nowU.S. Pat. No. 6,411,852; Ser. No. 09/436,455 Devices for Modification ofAirways by Transfer of Energy. The entirety of each of theaforementioned applications is incorporated by reference herein.

The treatment of an airway with the treatment device may involve placinga visualization system such as an endoscope or bronchoscope into theairways. The treatment device is then inserted through or next to thebronchoscope or endoscope while visualizing the airways. Alternatively,the visualization system may be built directly into the treatment deviceusing fiber optic imaging and lenses or a CCD and lens arranged at thedistal portion of the treatment device. The treatment device may also bepositioned using radiographic visualization such as fluoroscopy or otherexternal visualization means. The treatment device which has beenpositioned with a distal end within an airway to be treated is energizedso that energy is applied to the tissue of the airway walls in a desiredpattern and intensity. The distal end of the treatment device may bemoved through the airway in a uniform painting like motion to expose theentire length of an airway to be treated to the energy. The treatmentdevice may be passed axially along the airway one or more times toachieve adequate treatment. The “painting-like” motion used to exposedthe entire length of an airway to the energy may be performed by movingthe entire treatment device from the proximal end either manually or bymotor. Alternatively, segments, stripes, rings or other treatmentpatterns may be used.

According to one variation of the invention, the energy is transferredto or from an airway wall in the opening region of the airway,preferably within a length of approximately two times the airwaydiameter or less, and to wall regions of airways distal to bifurcationsand side branches, preferably within a distance of approximately twicethe airway diameter or less. The invention may also be used to treatlong segments of un-bifurcated airway.

The invention includes a method of advancing a treatment device into alung and treating the lung with the device to, at least, reduce theability of the lung to produce at least one symptom of reversibleobstructive pulmonary disease. It is contemplated that the treatment mayreduce all of the symptoms of reversible obstructive disease.Alternatively, the treatment may be selected to address specificsymptoms of the disease. It is also intended that the treatment of thelung may sufficiently reduce the symptoms of reversible obstructivepulmonary disease such that the patient is able to function as thosefree from the disease. Alternatively, the treatment may be such that thesymptoms are reduced to allow the patient to more easily manage thedisease. It is also intended that the effects of the treatment may beeither long term or short term with repeating treatment necessary tosuppress the symptoms.

The methods of the invention described herein may be performed while thelung is experiencing natural symptoms of reversible obstructivepulmonary disease. One such example is where an individual, experiencingan asthma attack, or acute exacerbation of asthma or COPD, undergoestreatment to improve the individual's ability to breath. In such a case,the treatment, called ‘rescue,’ seeks to provide immediate relief forthe patient.

The method may also include the steps of locating one or more treatmentsites within an airway of the lung, selecting one of the treatment sitesfrom the locating step and treating at least one of the selectedtreatment sites. As mentioned above, these steps may be, but are notnecessarily, performed while the lung is experiencing symptoms ofreversible obstructive pulmonary disease.

The invention may further comprise the step of stimulating the lung toproduce at least one artificially induced symptom of reversibleobstructive pulmonary disease. For example, stimulation of the lungwould preferably increase the resistance to airflow within the lung,constrict airways within the lung, inflame/irritate airway tissues,increase edema and/or increase the amount of mucus plugging of theairway. Stimulation of the lung may occur at any point during theprocedure or before the procedure. For example, the lung may bestimulated either prior to or after, the step of locating a treatmentsite. If the lung is stimulated prior to the step of locating atreatment site, the reaction of the stimulated tissue within the lungmay be useful in determining which locations are to be selected astreatment sites. The lung tissue or airway tissue within the lung may bestimulated by a variety of methods including but not limited topharmacological stimulation, (e.g., histamine, methacholine, or otherbronchoconstricting agents, etc.), electrical stimulation, mechanicalstimulation, or any other stimuli causing obstructive pulmonarysymptoms. For example, electrical stimulation may comprise exposingairway tissue to electrical field stimulation. An example of suchparameters include 15 VDC, 0.5 ms pulses, 0.5-16 Hz, and 70 VDC, 2-3 mspulses, 20 HZ.

The locating step described above may be performed using a non-invasiveimaging technique, including but not limited to, a bronchogram, magneticresonance imaging, computed tomography, radiography (e.g., x-ray), andventilation perfusion scans.

The invention further includes the steps of testing the lung for atleast one pre-treatment pulmonary function value prior to treating thelung with the device. After the lung is treated, the lung is re-testedfor at least one post-treatment pulmonary function value. Naturally, thetwo pulmonary function values may be compared to estimate the effect ofthe treatment. The invention may also include treating additional sitesin the lung after the re-testing step to at least reduce the effect ofat least one symptom of reversible obstructive pulmonary disease. Theinvention may also include stimulating the lung to produce at least oneartificially induced symptom of reversible obstructive pulmonarydisease. As mentioned above, the stimulation of the lung may occur atany point during, or prior to, the procedure. For example, stimulationof the lung may occur prior to the step of testing the lung forpre-treatment pulmonary values. In this case, the values would bedeterminative of pulmonary function values of a lung experiencingsymptoms of reversible obstructive pulmonary disease. Accordingly, theobjective is to treat the lung until acceptable pulmonary functionvalues are obtained. One benefit of such a procedure is that the effectof the treatment on the patient is more readily observed as compared tothe situation where a patient, having previously been treated, must waitfor an attack of reversible obstructive pulmonary disease to determinethe efficacy of the treatment.

Pulmonary function values are well known in the art. The following is anexample of pulmonary function values that may be used. Other pulmonaryfunction values, or combinations thereof, are intended to be within thescope of this invention. The values include, but are not limited to, FEV(forced expiratory volume), FVC (forced vital capacity), FEF (forcedexpiratory flow), Vmax (maximum flow), PEFR (peak expiratory flow rate),FRC (functional residual capacity), RV (residual volume), TLC (totallung capacity).

FEV measures the volume of air exhaled over a pre-determined period oftime by a forced expiration immediately after a full inspiration. FVCmeasures the total volume of air exhaled immediately after a fullinspiration. Forced expiratory flow measures the volume of air exhaledduring a FVC divided by the time in seconds. Vmax is the maximum flowmeasured during FVC. PEFR measures the maximum flow rate during a forcedexhale starting from full inspiration. RV is the volume of air remainingin the lungs after a full expiration.

The locating step described above may also comprise identifyingtreatment sites within the airway being susceptible to a symptom ofreversible obstructive pulmonary disease. For example, symptoms mayinclude, but are not limited to, airway inflammation, airwayconstriction, excessive mucous secretion, or any other asthmaticsymptom. Stimulation of the lung to produce symptoms of reversibleobstructive pulmonary disease may assist in identifying ideal treatmentsites.

As noted above, the method of the present invention may includestimulating the lung to produce at least one artificially inducedsymptom of reversible obstructive pulmonary disease and further includethe step of evaluating the result of stimulation of the lung. Forexample, the evaluating step may include visually evaluating the effectof the stimulating step on the airway using a bronchoscope with avisualization system or by non-invasive imaging techniques, such asthose describe herein. The evaluating step may include measuringpressure changes in the airway before and after the stimulating step.Pressure may be measured globally (e.g., within the entire lung), orlocally (e.g., within a specific section of the lung such as an airwayor alveolar sac.) Also, the evaluating step may comprise measuring theelectrical properties of the tissue before and after the stimulatingstep. The invention may also include evaluating the results of thestimulating step by combining any of the methods previously mentioned.Also, the invention may further comprise the step of selecting at leastone treatment parameter based upon the results of the evaluating step.Such treatment parameters may include, but are not limited to, durationof treatment, intensity of treatment, temperature, amount of tissuetreated, depth of treatment, etc.

The method may also include the step of determining the effect of thetreatment by visually observing lung, airway or other such tissue forblanching of the tissue. The term “blanching” is intended to include anyphysical change in tissue that is usually, but not necessarily,accompanied by a change in the color of the tissue. One example of suchblanching is where the tissue turns to a whitish color after thetreatment of application of energy.

The invention may also include the step of monitoring impedance across atreated area of tissue within the lung. Measuring impedance may beperformed in cases of monopolar or bipolar energy delivery devices.Additionally, impedance may be monitored at more than one site withinthe lungs. The measuring of impedance may be, but is not necessarily,performed by the same electrodes used to deliver the energy treatment tothe tissue. Furthermore, the invention includes adjusting the treatmentparameters based upon the monitoring of the change in impedance afterthe treatment step. For example, as the energy treatment affects theproperties of the treated tissue, measuring changes in impedance mayprovide information useful in adjusting treatment parameters to obtain adesired result.

Another aspect of the invention includes advancing a treatment deviceinto the lung and treating lung tissue to at least reduce the ability ofthe lung to produce at least one symptom of reversible obstructivepulmonary disease and further comprising the step of sub-mucosal sensingof the treatment to the lung tissue. The sub-mucosal sensing may beinvasive such as when using a probe equipped to monitor temperature,impedance, and/or blood flow. Or, the sub-mucosal sensing may benon-invasive in such cases as infra-red sensing.

The invention may also include using the treatment device to depositradioactive substances at select treatment sites within the lung. Theradioactive substances, including, but not limited to Iridium (e.g.¹⁹²Ir.) either treat the lung tissue over time or provide treatment uponbeing deposited.

The invention also includes scraping epithelial tissue from the wall ofan airway within the lung prior to advancing a treatment device into thelung to treat the lung tissue. The removal of the epithelial tissueallows the device to treat the walls of an airway more effectively. Theinvention further comprises the step of depositing a substance on thescraped wall of the airway after the device treats the airway wall. Thesubstance may include epithelial tissue, collagen, growth factors, orany other bio-compatible tissue or substance, which promotes healing,prevent infection, and/or assists in the clearing of mucus.Alternatively, the treatment may comprise the act of scraping epithelialtissue to induce yield the desired response.

The invention includes using the treating device to pre-treat the lungto at least reduce the ability of the lung to produce at least onesymptom of reversible obstructive pulmonary disease prior to thetreating step. At least one of the parameters of the pre-treating stepmay differ than one of the parameters of the treating step. Suchparameters may include time, temperature, amount of tissue over whichtreatment is applied, amount of energy applied, depth of treatment, etc.

The invention may also include advancing the treatment device into thelung and treating the lung tissue in separate stages. One of thebenefits of dividing the treating step into separate stages is that thehealing load of the patient is lessened. Dividing of the treating stepmay be accomplished by treating different regions of the lung atdifferent times. Or, the total number of treatment sites may be dividedinto a plurality of groups of treatment sites, where each group oftreatment sites is treated at a different time. The amount of timebetween treatments may be chosen such that the healing load placed onthe lungs is minimized.

The invention may also include advancing a treatment device into thelung, treating the lung with the device and sensing movement of the lungto reposition the treatment device in response to the movement. Thissensing step accounts for the tidal motion of the lung during breathingcycles or other movement. Taking into account the tidal motion allowsimproved accuracy in repositioning of the device at a desired target.

The invention may also include the additional step of reducing orstabilizing the temperature of lung tissue near to a treatment site.This may be accomplished for example, by injecting a cold fluid intolung parenchyma or into the airway being treated, where the airway isproximal, distal, or circumferentially adjacent to the treatment site.The fluid may be sterile normal saline, or any other bio-compatiblefluid. The fluid may be injected into treatment regions within the lungwhile other regions of the lung normally ventilated by gas. Or, thefluid may be oxygenated to eliminate the need for alternate ventilationof the lung. Upon achieving the desired reduction or stabilization oftemperature the fluid may be removed from the lungs. In the case where agas is used to reduce temperature, the gas may be removed from the lungor allowed to be naturally exhaled. One benefit of reducing orstabilizing the temperature of the lung may be to prevent excessivedestruction of the tissue, or to prevent destruction of certain types oftissue such as the epithelium, or to reduce the systemic healing loadupon the patient's lung.

Also contemplated as within the scope of the invention is the additionalstep of providing therapy to further reduce the effects of reversibleobstructive pulmonary disease or which aids the healing process aftersuch treatment. Some examples of therapy include, drug therapy, exercisetherapy, and respiratory therapy. The invention further includesproviding education on reversible obstructive pulmonary diseasemanagement techniques to further reduce the effects of the disease. Forexample, such techniques may be instruction on lifestyle changes,self-monitoring techniques to assess the state of the disease, and/ormedication compliance education.

There may be occurrences where it is necessary to reverse the effects ofthe treatment described herein. Accordingly, the invention furtherincludes a method for reversing a treatment to reduce the ability of thelung to produce at least one symptom of reversible obstructive pulmonarydisease comprising the step of stimulating re-growth of smooth muscletissue. The re-stimulation of the muscle may be accomplished by the useof electro-stimulation, exercising of the muscle and/or drug therapy.

The invention further includes methods of evaluating individuals havingreversible obstructive pulmonary disease, or a symptom thereof, as acandidate for a procedure to reduce the ability of the individual's lungto produce at least one symptom of reversible obstructive pulmonarydisease. The method comprises the steps of assessing the pulmonarycondition of the individual, comparing the pulmonary condition to acorresponding pre-determined state, and evaluate the individual as acandidate based upon the comparison.

In assessing the pulmonary condition, the method may comprise the stepsof performing pulmonary function tests on the individual to obtain apulmonary function value which is compared to a predetermined value.Examples of pre-determined values are found above.

The method of evaluating may further include the step of determining howthe individual's tissue will react to treatment allowing the treatmentto be tailored to the expected tissue response.

The method of evaluating may further comprises the step of pulmonaryfunction testing using a gas, a mixture of gases, or a composition ofseveral mixtures of gases to ventilate the lung. The difference inproperties of the gases may aid in the pulmonary function testing. Forexample, comparison of one or more pulmonary function test values thatare obtained with the patient breathing gas mixtures of varyingdensities may help to diagnose lung function. Examples of such mixturesinclude air, at standard atmospheric conditions, and a mixture of heliumand oxygen. Additional examples of pulmonary testing include tests thatmeasure capability and evenness of ventilation given diffusion ofspecial gas mixtures. Other examples of gases used in the describedtests, include but are not limited to, nitrogen, carbon monoxide, carbondioxide, and a range of inert gases.

The method of evaluating may also include the step of sub-mucosalimaging of the airway wall to determine if the individual will benefitfrom treatment and/or procedure effectiveness. Sub-mucosal imaging maybe accomplished by performing minimally invasive, high resolution,real-time optical coherence tomography (OCT) imaging of airway mucosa,for example via a flexible bronchoscope. OCT is a high-resolutionimaging technique (e.g., about 2 μm to about 10 μm) which is capable ofgenerating real-time, near-histological, cross-sectional images oftissue up to a depth of about 1 mm to about 2 mm. OCT measuresbackscattered infrared light intensity using coherence interferometry toconstruct topographical tissue images. Sub-mucosal imaging may also beaccomplished by a variety of other invasive and non-invasive imagingtechniques. For example microscopy techniques may be utilized, such asconfocal microscopy or reflectance microscopy, which are imagingtechniques that produce high resolution images and 3-D reconstructionsof tissue at various depths. Further, ultrasound imaging may also beemployed to perform the evaluating step. Still further, hyperpolarizedhelium may be fed into the lung in conjunction with non-invasivecomputed tomography (CT), magnetic resonance imaging (MRI), or positronemission tomography (PET) imaging to evaluate suitable patients fortreatment.

The invention may also comprise the step of stimulating the lung toproduce at least one artificially induced symptom of reversibleobstructive pulmonary disease. Stimulating the symptoms of the diseasein an individual allows the individual to be evaluated as the individualexperiences the symptoms thereby allowing appropriate adjustment of thetreatment.

The method of evaluating may also comprise the step of obtainingclinical information from the individual and accounting for the clinicalinformation for treatment.

The method may further comprise the selection of a patient for treatmentbased upon a classification of the subtype of the patient's disease. Forexample, in asthma there are a number of ways to classify the diseasestate. One such method is the assessment of the severity of the disease.An example of a classification scheme by severity is found in the NHLBIExpert Panel 2 Guidelines for the Diagnosis and Treatment of Asthma.Another selection method may include selecting a patient by the type oftrigger that induces the exacerbation. Such triggers may be classifiedfurther by comparing allergic versus non-allergic triggers. Forinstance, an exercise induced bronchospasm (EIB) is an example of anon-allergenic trigger. The allergic sub-type may be further classifiedaccording to specific triggers (e.g., dust mites, animal dander, etc.).Another classification of the allergic sub-type may be according tocharacteristic features of the immune system response such as levels ofIgE (a class of antibodies that function in allergic reactions, alsocalled immunoglobulin). Yet another classification of allergic sub-typesmay be according to the expression of genes controlling certaininterleukins (e.g., IL-4, IL-5, etc.) which have been shown to play akey role in certain types of asthma.

The invention further comprises methods to determine the completion ofthe procedure and the effectiveness of the reduction in the lung'sability to produce at least one symptom of reversible obstructivepulmonary disease. This variation of the invention comprises assessingthe pulmonary condition of the individual, comparing the pulmonarycondition to a corresponding predetermined state, and evaluating theeffectiveness of the procedure based on the comparison. The inventionmay also comprise the steps of performing pulmonary function tests onthe individual to obtain at least one pulmonary function value, treatingthe lung to at least reduce the ability of the lung to produce at leastone symptom of reversible obstructive pulmonary disease, performing apost-procedure pulmonary function tests on the individual to obtain atleast one post pulmonary function value and comparing the two values.

This variation of the invention comprises obtaining clinicalinformation, evaluating the clinical information with the results of thetest to determine the effectiveness of the procedure. Furthermore, thevariation may include stimulating the lung to produce a symptom ofreversible obstructive pulmonary disease, assessing the pulmonarycondition of the patient, then repeating the stimulation before thepost-procedure pulmonary therapy. These steps allow comparison of thelung function when it is experiencing symptoms of reversible obstructivepulmonary disease, before and after the treatment, thereby allowing foran assessment of the improved efficiency of the lung during an attack ofthe disease.

The invention herein is described by examples and a desired way ofpracticing the invention is described. However, the invention as claimedherein is not limited to that specific description in any manner.Equivalence to the description as hereinafter claimed is considered tobe within the scope of protection of this patent.

What is claimed is:
 1. A method of treating an individual havingreversible obstructive pulmonary disease to reduce an ability of a lungof the individual to produce a reversible obstructive pulmonary diseasesymptom, the method comprising: assessing a pulmonary condition of theindividual; comparing the pulmonary condition to a correspondingpredetermined state; evaluating the individual based on the comparing ofthe pulmonary condition; and treating an airway of the lung with anenergy transfer device, wherein treating the airway comprises: advancingan energy transfer device into the airway; and actuating the energytransfer device to effect patterned energy transfer at multiple spacedlocations within the airway, wherein the energy transfer alters theability of the lung to produce the reversible obstructive pulmonarydisease symptom.
 2. The method of claim 1, wherein treating the airwaycomprises delivering energy to a wall of the lung airway.
 3. The methodof claim 1, further comprising: performing a pulmonary function test onthe individual to obtain a pulmonary function value; comparing thepulmonary function value to a corresponding predetermined pulmonaryfunction value; and evaluating the individual based upon the comparing.4. The method of claim 3, wherein the pulmonary function value comprisesa forced expiratory volume, forced vital capacity, forced expiratoryflow, maximum flow, peak expiratory flow rate, functional residualcapacity, residual volume, total lung capacity, or a combinationthereof.
 5. The method of claim 1, wherein assessing further comprisesdetermining a subtype of asthma.
 6. The method of claim 5, whereindetermining further comprises assessing a severity of the asthma in theindividual.
 7. The method of claim 5, wherein determining furthercomprises assessing a trigger that induces the asthma in the individual.8. The method of claim 5, wherein determining further comprisesassessing a characteristic feature of an immune system response in theindividual having asthma.
 9. The method of claim 5, wherein determiningfurther comprises assessing an expression of genes controlling aninterleukin in the individual.
 10. The method of claim 1, furthercomprising stimulating the lung to produce an artificially inducedsymptom of reversible obstructive pulmonary disease prior to theassessing the pulmonary condition.
 11. The method of claim 1, furthercomprising obtaining clinical information from the individual, whereinevaluating further comprises accounting for the clinical information.12. The method of claim 1, further comprising determining how tissue ofthe individual will react to treatment, wherein evaluating furthercomprises accounting for a reaction of tissue to treatment.
 13. Themethod of claim 1, further comprising feeding a gas into the lung,wherein the gas has properties which aid in the assessment of thepulmonary condition.
 14. The method of claim 13, further comprisingfeeding another gas into the lung, wherein each gas has differentproperties which aid in the assessment of the pulmonary condition. 15.The method of claim 13, wherein the gas comprises helium, oxygen,nitrogen, carbon monoxide, carbon dioxide, or an inert gas.
 16. Themethod of claim 1, further comprising assessing a post-procedurepulmonary condition and comparing the pulmonary condition with thepost-procedure pulmonary condition to determine an effect of thetreatment procedure.
 17. The method of claim 1, wherein assessingfurther comprises sub-mucosal imaging of the lung airway.
 18. The methodof claim 1, wherein the energy transfer device is actuated multipletimes in a repeating pattern.
 19. The method of claim 1, furthercomprising actuating the energy transfer device in a plurality ofairways in differing regions of the lung.
 20. The method of claim 1,further comprising the step of electrically stimulating the lung priorto the treating step.